Methods for fluid mixing systems with tiltable support housing

ABSTRACT

A method for mixing a fluid includes: dispensing a first volume of a fluid into a flexible container, the flexible container being at least partially disposed within the chamber of a support housing; repeatedly moving the support housing and the flexible container contained therein so as to mix the first volume of fluid within the flexible container; adding further fluid into the flexible container after moving the support housing to form a second volume of fluid; and manipulating a mixing element within the flexible container so as to mix the second volume of fluid.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.14/405,126, filed Dec. 2, 2014, now U.S. Pat. No. 10,035,116, which is aUS nationalization of PCT Application No. PCT/US2013/027819, filed Feb.26, 2013, which claims the benefit of U.S. Provisional application Ser.No. 61/660,608, filed on Jun. 15, 2012, and which are herebyincorporated herein by specific reference.

BACKGROUND OF THE INVENTION 1. The Field of the Invention

The present invention relates to methods of using fluid mixing systemsthat can function as a fermentor or bioreactor and, more specifically,to methods for fluid mixing systems having a support housing that can beselectively tilted for assembly and/or rocked or otherwise reciprocallymoved for mixing fluid.

2. The Relevant Technology

The biopharmaceutical industry uses a broad range of mixing systems fora variety of processes such as in the preparation of media and buffersand in the growing, mixing and suspension of cells and microorganisms.Some conventional mixing systems, including bioreactors and fermentors,comprise a flexible bag disposed within a rigid support housing. A driveshaft projects into the flexible bag and has an impeller mountedthereon. Rotation of the drive shaft and impeller facilitates mixingand/or suspension of the fluid contained within flexible bag.

Depending on the desired processing and batch size, the support housingand the flexible bag contained therein can be relatively tall. Having atall support housing can produce a number of complications. For example,a tall support housing can preclude passing the support housing throughselect doorways and thereby limit where the mixing system can beoperated. Furthermore, when using tall support housings, it can bedifficult to insert the flexible bag into the support housing and adjustthe position thereof. This commonly requires the operator to stand on aladder which can be precarious. In addition, where the mixing system isoperating in a room with a relatively low ceiling, a tall supporthousing can limit the ability to vertically advance a drive shaft downinto the flexible bag within the support housing, thereby furtherlimiting where the mixing system can be used.

The impeller is typically fixed at the end of the drive shaft and isdesigned to remain at a substantially fixed position which is optimalfor mixing a narrowly defined volume of solution in the flexible bag. Toenable homogeneous mixing of larger volumes of solution, larger bags areused that have an impeller positioned at a location that is optimal forthat size of bag.

In some processing procedures it can be desirable to initially mixsolutions at a low volume and then progressively increase the volume ofthe solution. For example, this is a common procedure used withbioreactors for growing cells. The process typically entails dispensinga seed inoculum in a growth media contained within a relatively smallbag or container and then transferring the solution to progressivelylarger bags where additional media is added as the cells grow andmultiple. This process is repeated until a final desired volume isachieved. By transferring the solution to different sized bags orcontainers, which each have a corresponding mixer, the operator canensure homogeneous mixing of each of the different volumes of solution.Maintaining homogeneous mixing in a bioreactor or fermentor is importantto ensure proper feeding and mass transfer of gasses to the cells ormicroorganisms.

Although the above process of moving solutions to different sized bagsto maintain proper mixing and suspension is functional, the procedurehas some shortcomings. For example, the necessity of stepping todifferent sized bags is labor intensive, time consuming, and has highmaterial costs in that each bag is typically discarded after use.Furthermore, transferring between different bags produces some mixingdown-time which can influence cell growth. In addition, the necessity ofshifting between bags increases the risk of contamination to thesolution and potential damage to the cells.

Accordingly, what is needed in the art are methods and/or systems forsolving all or at least some of the above problems associated withmixing systems having a tall support housing and/or transferringsolutions between multiple different size bags to maintain homogeneousmixing.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention will now be discussed withreference to the appended drawings. It is appreciated that thesedrawings depict only typical embodiments of the invention and aretherefore not to be considered limiting of its scope.

FIG. 1 is a perspective view of an inventive fluid mixing system;

FIG. 2 is a perspective view of a container assembly of the mixingsystem shown in FIG. 1;

FIG. 3 is a elevated side view of an impeller assembly of the containerassembly shown in FIG. 2 with a drive shaft that is removably receivablewithin the impeller assembly;

FIG. 4 is a cross sectional side view of a rotational assembly of theimpeller assembly shown in FIG. 3;

FIG. 5 is a partially exploded view of the impeller assembly, driveshaft, and drive motor assembly of the mixing system shown in FIG. 1;

FIG. 6 is a perspective view of the support housing shown in FIG. 1tilted to a second position;

FIG. 7 is a elevated front view of an alternative embodiment of thecontainer assembly shown in FIG. 2;

FIG. 8 is an alternative embodiment of a fluid mixing system having amotor and a corresponding controller for rocking of the support housing;

FIG. 9 is a perspective view of the fluid mixing system shown in FIG. 8with the support housing in a forward tilt position;

FIG. 10 is a perspective view of the fluid mixing system shown in FIG. 8with the support housing in a rearward tilt position;

FIG. 11 is a perspective view of an alternative embodiment of a fluidmixing system having a rack for adjustably tilting and elevating thedrive motor assembly;

FIG. 12 is a perspective view of the fluid mixing system shown in FIG.11 with the drive motor assembly tilted to a second position; and

FIG. 13 is a perspective view of an alternative embodiment of a fluidmixing system wherein the support housing is resting on a shaker table.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

As used in the specification and appended claims, directional terms,such as “top,” “bottom,” “left,” “right,” “up,” “down,” “upper,”“lower,” “proximal,” “distal” and the like are used herein solely toindicate relative directions and are not otherwise intended to limit thescope of the invention or claims.

The present invention relates to systems and methods for mixing fluidssuch as solutions or suspensions. The systems can be commonly used asbioreactors or fermentors for culturing cells or microorganisms. By wayof example and not by limitation, the inventive systems can be used inculturing bacteria, fungi, algae, plant cells, animal cells, protozoan,nematodes, and the like. The systems can accommodate cells andmicroorganisms that are aerobic or anaerobic and are adherent ornon-adherent. The systems can also be used in association with theformation and/or treatment of solutions and/or suspensions that are forbiological purposes, such as media, buffers, or reagents. For example,the systems can be used in the formation of media where sparging is usedto control the pH of the media through adjustment of thecarbonate/bicarbonate levels with controlled gaseous levels of carbondioxide. The systems can also be used for mixing powders or othercomponents into a liquid where sparging is not required and/or where thesolution/suspension is not for biological purposes.

Depicted in FIG. 1 is one embodiment of an inventive mixing system 10incorporating features of the present invention. In general, mixingsystem 10 comprises a stand 12, a support housing 14 that is pivotablymounted to stand 12, a container assembly 16 that is supported withinsupport housing 14, a drive motor assembly 15 mounted on support housing14 and a drive shaft 17 (FIG. 3) that extends between drive motorassembly 15 and container assembly 16. Container assembly 16 houses thefluid that is mixed and otherwise processed. The various components ofmixing system 10 will now be discussed in greater detail.

As depicted in FIG. 2, container assembly 16 comprises a container 18having a side 20 that extends from an upper end 22 to an opposing lowerend 24. Upper end 22 terminates at an upper end wall 33 while lower end24 terminates at a lower end wall 34. Container 18 also has an interiorsurface 26 that bounds a compartment 28. Compartment 28 is configured tohold a fluid. In the embodiment depicted, container 18 comprises aflexible bag that is comprised of one or more sheets of a flexible,water impermeable material such as a low-density polyethylene or otherpolymeric film having a thickness in a range between about 0.1 mm toabout 5 mm with about 0.2 mm to about 2 mm being more common. Otherthicknesses can also be used. The material can be comprised of a singleply material or can comprise two or more layers which are either sealedtogether or separated to form a double wall container. Where the layersare sealed together, the material can comprise a laminated or extrudedmaterial. The laminated material comprises two or more separately formedlayers that are subsequently secured together by an adhesive. Examplesof extruded material that can be used in the present invention includethe Thermo Scientific CX3-9 and Thermo Scientific CX5-14 films availablefrom Thermo Fisher Scientific. The material can be approved for directcontact with living cells and be capable of maintaining a solutionsterile. In such an embodiment, the material can also be sterilizablesuch as by ionizing radiation.

In one embodiment, container 18 can comprise a two-dimensional pillowstyle bag. In another embodiment, container 18 can be formed from acontinuous tubular extrusion of polymeric material that is cut tolength. The ends can be seamed closed or panels can be sealed over theopen ends to form a three-dimensional bag. Three-dimensional bags notonly have an annular side wall but also a two dimensional top end walland a two dimensional bottom end wall. Three dimensional containers cancomprise a plurality of discrete panels, typically three or more, andmore commonly four to six. Each panel is substantially identical andcomprises a portion of the side wall, top end wall, and bottom end wallof the container. Corresponding perimeter edges of each panel are seamedtogether. The seams are typically formed using methods known in the artsuch as heat energies, RF energies, sonics, or other sealing energies.

In alternative embodiments, the panels can be formed in a variety ofdifferent patterns. Further disclosure with regard to one method ofmanufacturing three-dimensional bags is disclosed in United StatesPatent Publication No. US 2002-0131654 A1, published Sep. 19, 2002 whichis incorporated herein by specific reference in its entirety.

It is appreciated that container 18 can be manufactured to havevirtually any desired size, shape, and configuration. For example,container 18 can be formed having a compartment sized to 10 liters, 30liters, 100 liters, 250 liters, 500 liters, 750 liters, 1,000 liters,1,500 liters, 3,000 liters, 5,000 liters, 10,000 liters or other desiredvolumes. The size of the compartment can also be in the range betweenany two of the above volumes. Although container 18 can be any shape, inone embodiment container 18 is specifically configured to be generallycomplementary to the chamber on support housing 14 in which container 18is received so that container 18 is properly supported within thechamber.

Although in the above discussed embodiment container 18 is depicted as aflexible bag, in alternative embodiments it is appreciated thatcontainer 18 can comprise any form of collapsible container ordisposable container. Container 18 can also be transparent or opaque.

Continuing with FIG. 2, formed on container 18 are a plurality of ports30 at upper end 22 and a plurality of ports 31 at lower end 24. Each ofports 30, 31 communicate with compartment 28. Although only a few ports30, 31 are shown, it is appreciated that container 18 can be formed withany desired number of ports 30, 31 and that ports 30, 31 can be formedat any desired location on container 18. Ports 30, 31 can be the sameconfiguration or different configurations and can be used for a varietyof different purposes. For example, ports 30 can be coupled with fluidlines for delivering media, cell cultures, and/or other components intocontainer 18 and withdrawing fluid from container 18. Ports 30 can alsobe used for delivering gas to container 18, such as through a sparger,and withdrawing gas from container 18.

Ports 30, 31 can also be used for coupling probes and/or sensors tocontainer 18. For example, when container 18 is used as a bioreactor orfermentor for growing cells or microorganisms, ports 30, 31 can be usedfor coupling probes such as temperatures probes, pH probes, dissolvedoxygen probes, and the like. Various optical sensors and other types ofsensors can also be attached to ports 30, 31. Examples of ports 30, 31and how various probes, sensors, and lines can be coupled thereto isdisclosed in United States Patent Publication No. 2006-0270036,published Nov. 30, 2006 and United States Patent Publication No.2006-0240546, published Oct. 26, 2006, which are incorporated herein byspecific reference in their entirety. Ports 30, 31 can also be used forcoupling container 18 to secondary containers, to condenser systems, andto other desired fittings.

Also formed on side 20 below ports 31 so as to be adjacent to lower endwall 34 is a drain port 38 having a drain line 39 coupled thereto. Aswill be discussed below in greater detail, as a result of being able totilt support housing 14 containing container 18, improved or a morecomplete draining can be accomplished through drain line 39 relative totraditional draining.

Mounted on lower end wall 34 is a sparger 36 having a gas line 37coupled thereto. Sparger 36 is designed to deliver gas bubbles to theculture or other fluid within container 18 for oxygenating and/orregulating content of various gases within the culture/fluid. As needed,a second or more spargers can be mounted on lower end wall 34. Thespargers can be the same or different configurations. For example, onesparger can be designed to deliver small bubbles for oxygenating while asecond sparger can be designed to deliver larger bubbles for strippingCO₂ from the culture/fluid. In some forms of the invention, one of thespargers can be an open tube or a tube with a porous frit withrelatively large pores, while the other sparger can be a tube with aporous frit with relatively small pores. The sparger can also comprise aperforated or porous membrane that is mounted on the end of a port or onthe interior surface of lower end wall 34 so as to extend over a port.It is appreciated that spargers come in a variety of differentconfigurations and that any type of spargers can be used as desired oras appropriate for the expected culture volumes, cells, fluids and otherconditions. In some uses of mixing system 10, a sparger may not berequired and thus sparger 36 can be eliminated.

It is appreciated that the various gas lines, fluid lines, spraginglines, drain lines and/or the like can be coupled to container 18 at thetime of manufacture so that they can be sterilized concurrently withcontainer 18. Alternatively, the lines can be connected to container 18either prior to or after inserting container 18 into support housing 14or prior to or after container 18 is tilted or rocked within supporthousing 14, as will be discussed below. The lines are typically longenough so that support housing 14 containing container 18 can be rockedor tilted during operation without interfering with the operation of thelines. In other embodiments, some lines may be disconnected fromcontainer 18 prior to tilting or rocking of support housing 14 and thenreconnected after tiling or rocking of support housing 14 with container18. The lines can be connected to container 18 using commonly knownaseptic connectors.

Container assembly 16 further comprises an impeller assembly 40. Asdepicted in FIG. 3, impeller assembly 40 comprises an elongated tubularconnector 42 having a rotational assembly 48 mounted at one end and animpeller 64 mounted on the opposing end. More specifically, tubularconnector 42 has a first end 44 and an opposing second end 46 with apassage 49 that extends therebetween. In one embodiment, tubularconnector 42 comprises a flexible tube such as a polymeric tube. Inother embodiments, tubular connector 42 can comprise a rigid tube orother tubular structure.

Rotational assembly 48 is mounted to first end 44 of tubular connector42. As depicted in FIG. 4, rotational assembly 48 comprises an outercasing 50 having an outwardly projecting annular sealing flange 52 andan outwardly projecting mounting flange 53. A tubular hub 54 isrotatably disposed within outer casing 50. One or more bearingassemblies 55 can be disposed between outer casing 50 and hub 54 topermit free and easy rotation of hub 54 relative to casing 50. Likewise,one or more seals 57 can be formed between outer casing 50 and hub 54 sothat during use an aseptic seal can be maintained between outer casing50 and hub 54.

Hub 54 has an interior surface 56 that bounds an opening 58 extendingtherethrough. As will be discussed below in greater detail, interiorsurface 56 includes an engaging portion 61 having a polygonal or othernon-circular transverse cross section so that a driver portion 180 ofdrive shaft 17 (FIG. 3) passing through opening 58 can engage engagingportion 61 and facilitate rotation of hub 54 by rotation of drive shaft17. Hub 54 can also comprise a tubular stem 60 projecting away fromouter casing 50. Returning to FIG. 3, hub 54 can couple with first end44 of tubular connector 42 by stem 60 being received within first end44. A pull tie, clamp, crimp or other fastener can then be used tofurther secure stem 60 to tubular connect 42 so that a liquid tight sealis formed therebetween. Other conventional connecting techniques canalso be used.

Impeller 64 comprises a central hub 66 having a plurality of blades 68radially outwardly projecting therefrom. In the embodiment depicted,blades 68 are integrally formed as a unitary structure with hub 66. Inother embodiments, blades 68 can be separately attached to hub 66. It isappreciated that a variety of different numbers and configurations ofblades 68 can be mounted on hub 66. Hub 66 has a first end 70 with ablind socket 72 formed thereat. Socket 72 typically has a noncirculartransverse cross section, such as polygonal, so that it can engage adriver portion 178 of drive shaft 17. Accordingly, as will be discussedbelow in greater detail, when driver portion 178 is received withinsocket 72, driver portion 178 engages with impeller 64 such thatrotation of drive shaft 17 facilities rotation of impeller 64.

Impeller 64 can be attached to connector 42 by inserting first end 70 ofhub 66 within connector 42 at second end 46. A pull tie, clamp, crimp,or other type of fastener can then be cinched around second end 46 ofconnector 42 so as to form a liquid tight sealed engagement betweenimpeller 64 and connector 42.

Turning to FIG. 2, rotational assembly 48 is secured to container 18 sothat tubular connector 42 and impeller 64 extend into or are disposedwithin compartment 28 of container 18. Specifically, in the depictedembodiment container 18 has an opening 74 at upper end 22. Sealingflange 52 of outer casing 50 is sealed around the perimeter edgebounding opening 74 so that hub 54 is aligned with opening 74. Tubularconnector 42 having impeller 64 mounted on the end thereof projects fromhub 54 into compartment 28 of container 18. In this configuration, outercasing 50 is fixed to container 18 but hub 54, and thus also tubularconnector 42 and impeller 64, can freely rotate relative to outer casing50 and container 18. As a result of rotational assembly 48 sealingopening 74, compartment 28 is sealed closed so that it can be used inprocessing sterile fluids.

As depicted in FIG. 3, impeller assembly 40 is used in conjunction withdrive shaft 17. In general drive shaft 17 comprises a head section 164and a shaft section 166 that can be coupled together by threadedconnection or other techniques. Alternatively, drive shaft 17 can beformed as a single piece member or from a plurality of attachablesections. Drive shaft 17 has a first end 168 and an opposing second end170. Formed at first end 168 is a frustoconical engaging portion 172that terminates at a circular plate 174. Notches 176 are formed on theperimeter edge of circular plate 174 and are used for engaging driveshaft 17 with drive motor assembly 15 as will be discussed below.

Formed at second end 170 of drive shaft 17 is driver portion 178. Driverportion 178 has a non-circular transverse cross section so that it canfacilitate locking engagement within hub 66 of impeller 64 as discussedabove. In the embodiment depicted, driver portion 178 has a polygonaltransverse cross section. However, other non-circular shapes can also beused. Driver portion 180 is also formed along drive shaft 17 towardfirst end 168. Driver portion 180 also has a non-circular transversecross section and is positioned so that it can facilitate lockingengagement within engaging portion 61 (FIG. 4) of rotational assembly 48as discussed above.

During use, as will be discussed below in further detail, drive shaft 17is advanced down through hub 54 of rotational assembly 48, throughtubular connector 42 and into hub 66 of impeller 64. As a result of theinterlocking engagement of driver portions 178 and 180 with hubs 66 and54, respectively, rotation of drive shaft 17 by drive motor assembly 15(FIG. 1) facilitates rotation of hub 54, tubular connector 42 andimpeller 64 relative to outer casing 50 of rotational assembly 48 andcontainer 18. As a result of the rotation of impeller 64, fluid withincontainer 18 is mixed.

It is appreciated that impeller assembly 40, drive shaft 17 and thediscrete components thereof can have a variety of differentconfiguration and can be made of a variety of different materials.Alternative embodiments of and further disclosure with respect toimpeller assembly 40, drive shaft 17, and the components thereof aredisclosed in U.S. Pat. No. 7,384,783, issued Jun. 10, 2008 and US PatentPublication No. 2011/0188928, published Aug. 4, 2011 which areincorporated herein in their entirety by specific reference.

Returning to FIG. 1, support housing 14 has a substantially cylindricalsidewall 82 that extends between an upper end 84 and an opposing lowerend 86. Lower end 86 has a floor 88 mounted thereto. As a result,support housing 14 has an interior surface 90 that bounds a chamber 92.An annular lip 94 is formed at upper end 84 and bounds an access opening96 to chamber 92. As discussed above, chamber 92 is configured toreceive container assembly 16 so that container 18 is supported therein.

Although support housing 14 is shown as having a substantiallycylindrical configuration, in alternative embodiments support housing 14can have any desired shape capable of at least partially bounding acompartment. For example, sidewall 82 need not be cylindrical but canhave a variety of other transverse, cross sectional configurations suchas polygonal, elliptical, or irregular. Furthermore, it is appreciatedthat support housing 14 can be scaled to any desired size. For example,it is envisioned that support housing 14 can be sized so that chamber 92can hold a volume of less than 50 liters, more than 10,000 liters or anyof the other volumes or range of volumes as discussed above with regardto container 18. Support housing 14 is typically made of metal, such asstainless steel, but can also be made of other materials capable ofwithstanding the applied loads of the present invention.

While support housing 14 can have any desired dimensions, in oneembodiment support housing 14 can be elongated with a relatively smalldiameter. Specifically, when mixing system 10 is used as a fermentor, itis desirable to have a high mixing rate of the culture within container18 to maintain consistent oxygenation and nutrient content throughoutthe culture. The mixing efficiency is increased by support housing 14and corresponding container 18 having a relatively small diameter sothat the culture is maintained relatively close to impeller 64. Becausethe diameter is relatively small, to enable batch processing attraditional volumes, the height of support housing 14 and correspondingcontainer 18 can be long relative to the diameter. Having a relativelytall support housing 14 and corresponding container 18 also increasesthe resident time of the sparged gas bubbles within container 18,thereby increasing the mass transfer of the gas into the fluid. Again,this has increased importance where mixing system 10 is used as afermentor.

By way of example and not by limitation, chamber 92 of support housing14 can have a central longitudinal axis 98 that extends through floor 88and access opening 96. Chamber 92 can have a maximum transverse diameterD that is normal to axis 98 and a height H that that extends alonglongitudinal axis 98 between floor 88 and access opening 96. Chamber 92can be made with diameter D being between about 15 cm to about 225 cmand a corresponding height H being between about 35 cm to about 500 cm.The ratio of height H to diameter D to can be in a range between about 1to about 10 with about 1.2 to about 4 and about 1.6 to about 3.3 beingmore common. In some embodiments, the ratio can be greater than 1.5, 2,2.5, 3, 4, or 5. Again, other dimensions and ratios can also be useddepending on the intended use for mixing system 10. It is appreciatedthat the diameters and heights as discussed above with regard to supporthousing 14 are also applicable to the diameter and height of container18 when positioned within support housing 14. In addition, by makingsupport housings 14 elongated with a relatively small diameter, mixingsystem 10 can be passed through normal or narrow doorways through whichtraditionally sized mixing system would not fit. As such, mixing systems10 can be used in a broader range of locations.

Extending through sidewall 82 of support housing 14 at lower end 86 areslots 100A and 100B that extend horizontally and are vertically spacedapart. Slots 100A and B are designed to receive corresponding rows ofports 31. As previously mentioned, any number of ports 31 can be formedon container 18. In turn, as also previously discussed, sensors, probes,fluid lines, and the like can be coupled with ports 31 so as tocommunicate with compartment 28 of container 18. A vertical slot 102also passes through sidewall 82 and extends down from slot 100B. In thisconfiguration, slot 102 terminates close to floor 88. Drain port 38and/or drain line 39 extend out through slot 102. In other embodiments,drain line 39 can extend out through other openings formed on sidewall82 or on floor 88. Drain line 39 is typically coupled to container 18through drain port 38 that is spaced apart from floor 88 but is locatedwithin 20 cm from floor 88 of support housing 14 and more commonlywithin 15 cm or 7 cm from floor 88. Other locations can also be used. Anopening 103 extends through floor 88 through which gas line 37 passesout.

In one embodiment of the present invention means are provided forregulating the temperature of the fluid that is contained withincontainer 18 when container 18 is disposed within support housing 14. Byway of example and not by limitation, sidewall 82 can be jacketed so asto bound one or more fluid channels that encircle sidewall 82 and thatcommunicate with an inlet port 104 and an outlet port 106. A fluid, suchas water or propylene glycol, can be pumped into the fluid channelthrough inlet port 104. The fluid then flows in a pattern aroundsidewall 82 and then exits out through outlet port 106.

By heating or otherwise controlling the temperature of the fluid that ispassed into the fluid channel, the temperature of support housing 14 canbe regulated which in turn regulates the temperature of the fluid withincontainer 18 when container 18 is disposed within support housing 14. Inan alternative embodiment, electrical heating elements can be mounted onor within support housing 14. The heat from the heating elements istransferred either directly or indirectly to container 18.Alternatively, other conventional means can also be used such as byapplying gas burners to support housing 14 or pumping the fluid out ofcontainer 18, heating the fluid and then pumping the fluid back intocontainer 18. When using container 18 as part of a bioreactor orfermentor, the means for heating can be used to heat the culture withincontainer 18 to a temperature in a range between about 30° C. to about40° C. Other temperatures can also be used.

Returning to FIG. 1, drive motor assembly 15 comprises a drive motor 112mounted to upper end 84 of support housing 14 by a bracket 114. Asupport arm 116 has a first end 118 that is pivotably mounted to drivemotor 112 and an opposing second end 120. As a result of support arm 116being pivotably mounted to drive motor 112, support arm 116 can bepivotably moved between a first position and a second position. In thefirst position, as shown in FIG. 1, support arm 116 projects over accessopening 96 of support housing 14 and second end 120 can be aligned withaxis 98. In the second position, as shown in FIG. 6, support arm 116 canbe pivoted so as to be spaced apart from axis 98 and, more commonly, sothat support arm 116 does not extend over or is not aligned with accessopening 96. As will be discussed below in greater detail, this pivotingof support arm 116 enables easier access to chamber 92 of supporthousing 14 for the insertion or removal of container assembly 16.Furthermore, by mounting drive motor 112 on the side of support housing14, as opposed to above support housing 14, mixing system 10 has a lowerheight so it can be used in rooms having a lower ceiling.

Turning to FIG. 5, disposed at second end 120 of support arm 116 is ahousing 124 having a front face 126. A U-shaped receiving slot 128 isrecessed on front face 126. An opening 130 extends down through secondend 120 of support arm 116 so as to communicate with receiving slot 128.Receiving slot 128 is bounded by an inside face 132 on which a U-shapedcatch slot 134 is recessed. A door 136 is hingedly mounted to housing124 and selectively closes the opening to receiving slot 128 from frontface 126.

A tubular motor mount 138 is rotatably secured within opening 130 on arm116 so as to align with receiving slot 128. Motor mount 138 bounds apassage 139 extending therethrough. Upstanding from motor mount 138 is alocking pin 140. A drive member 142 extends within arm 116 from drivemotor 112 to motor mount 138. Drive motor 112 engages with drive member142 so that the activation of drive motor 112 facilitates the rotationof motor mount 138 through drive member 142. Drive member 142 cancomprise a belt, gear, linkage, drive shaft or any other mechanism thatcan transfer energy from drive motor 112 to motor mount 138 tofacilitate select rotation of motor mount 138 relative to arm 116.

To facilitate attachment of rotational assembly 48 to housing 124, door136 is rotated to an open position and rotational assembly 48 ishorizontally slid into receiving slot 128 from front face 126 of housing124 so that mounting flange 53 of rotational assembly 48 is receivedwithin catch slot 134. Rotational assembly 48 is advanced into receivingslot 128 so that opening 58 of rotational assembly 48 (FIG. 4) alignswith passage 139 extending through motor mount 138. In this position,door 136 is moved to the closed position and secured in place by a latchor other locking mechanism so that rotational assembly 48 is locked todrive motor assembly 15.

Drive shaft 17 is configured to pass through motor mount 138 so thatengaging portion 172 of drive shaft 17 is retained within motor mount138 and locking pin 140 of motor mount 138 is received within notch 176of drive shaft 17. A cap 175 can then be threaded or otherwise securedonto motor mount 138 so as to secure drive shaft 17 in place. In thisconfiguration, rotation of motor mount 138 by drive motor 112facilitates rotation of drive shaft 17. Further discussion of drivemotor assembly 15 and how it engages with drive shaft 17 and alternativedesigns of drive motor assembly 15 are discussed in US PatentPublication No. 2011/0188928 which was previously incorporated herein byspecific reference.

Returning to FIG. 1, stand 12 comprises a base 186 that can directlyrest on a floor surface or can be supported on a floor surface by wheels188, adjustable legs 190, or the like. Upstanding from base 186 onopposing sides of support housing 14 are braces 192A and 192B. Supporthousing 14 is pivotably mounted to braces 192A and 192B. Specifically,each brace 192A and 192B has a collar 194 mounted on the end thereof.Axles 196 outwardly project from the opposing sides of sidewall 82 ofsupport housing 14 and are rotatably received within correspondingcollars 194. As such, support housing 14 can pivot relative stand 12 byaxles 196 rotating within collars 194. An axis 197 extends through axles196 about which support housing 14 rotates. A bearing can be disposedbetween each axle 196 and corresponding collars 194 to facilitate easeof rotation.

In the depicted configuration, support housing 14 can be pivoted from afirst position to a second position. In the first position, as shown inFIG. 1, longitudinal axis 98 of support housing 14 can be aligned with avertical axis 198. In the second position, as shown in FIG. 6, supporthousing 14 can be pivoted so that longitudinal axis 98 is disposed at anangle α relative to vertical axis 198. In one embodiment, supporthousing 14 can tilt forward and/or backward over an angle α of at least145° relative to vertical. In other embodiments, support housing 14 cantilt forward and/or backwards over an angle α of at least 130°, 100°,75°, 45°, or 15° relative to vertical. Other angles can also be used.

The ability to pivot support housing 14 produces a number of uniquebenefits. For example, by pivoting support housing 14 at approximately90°, it becomes easy for an operator to access chamber 92 of supporthousing 14 through access opening 96. The operator can thus easilyinsert, adjust, or remove container assembly 16 from chamber 92 whilestanding on the floor. This is particularly helpful where supporthousing 14 has an extended length that would normally require anoperator to access chamber 92 through the use of a ladder or othersupport structure. Slots 100 and 102 and opening 103 (FIG. 1) are alsoeasily accessed when support housing 14 is tilted to the second positionfor manipulating container 18 and aligning ports and related tubing. Inaddition to assisting in the placement of container assembly 16, thetilting of support housing 14 also assists in the placement of driveshaft 17 (FIG. 3). That is, it can be much easier to horizontally insertdrive shaft 17 through motor mount 138 while standing on the groundrather than trying to vertically elevate drive shaft 17 above supporthousing 14 while standing on a ladder or other platform.

In addition, mixing system 10 may be operated in a room with a ceilingthat is low relative to the height of support housing 14. In thissituation, the ceiling may be so low that it would be impossible tovertically raise drive shaft 17 above support housing 14 for insertionthrough motor mount 138. As such, the ability to tilt support housing 14broadens the locations in which mixing system 10 can be used.

Another benefit derived from the ability to tilt support housing 14 isthat it assists in the draining of container 18. For example, when fluidis drained out through a drain line extending through the floor oftraditional support housing, volumes of fluid can pool on the floorwithin the flexible container and not flow to the drain line. Forexample, the fluid can get trapped or blocked by folds of the container.The container must then be manually manipulated to try and get the fluidto flow to the drain line. This can be very difficult with largecontainers. In present invention, even if the fluid does initially poolon the floor, by tilting support housing 14, such as shown in FIG. 9,the fluid can be forced to flow to drain port 38 and out drain line 39.The flow of fluid through drain line 39 can be controlled by a valve 41(FIG. 2) coupled therewith. As such, embodiments of the inventive mixingsystem 10 enable a more complete draining or at least an easier drainingof fluid from container 18. When draining through drain line 39, supporthousing 14 is typically tilted so that longitudinal axis 98 is at anangle relative to vertical that is in a range between about 2° to about45° with about 5° to about 25° or about 5° to about 15° being morecommon. Other angles can also be used.

In one embodiment of the present invention, means are provided forreleasably locking support housing 14 relative to stand 12. By way ofexample and not by limitation, as depicted in FIG. 6, an opening 202extends through collar 194 while a plurality of radially spaced apartopenings 204 are formed on axial 196. When opening 202 and one ofopenings 204 align, a locking pin 206 can be passed into the alignedopenings for locking support housing 14 relative to stand 12. By usingthis configuration, support housing 14 can be locked in the verticalposition, as shown in FIG. 1, in a horizontal position, as shown in FIG.6, or at a variety of other angled orientations. It is appreciated thatthere are a variety of other locking mechanisms that can be used to locksupport housing 14 relative to stand 12. For example, differentfasteners, clamps, brakes, blocks, or other stopping mechanisms can bemounted at the junction between axle 196 and collar 194 or can bemounted at a separate location so as to directly secure support housing14 to prevent the pivoting thereof.

During use, locking pin 206 is removed or the other locking mechanism isreleased and support housing 14 is rotated to a desired orientationwhich is typically in a range between about 45° to about 135° relativeto vertical. Support arm 116 is then rotated to the second position(FIG. 6) so that access opening 96 to chamber 92 is freely exposed.Container assembly 16 (FIG. 1) is then manually positioned andorientated within chamber 92 of support housing 14 with the port, drainline, and sparge line being fed out through their corresponding openingand slots on support housing 14 as previously discussed.

Next, support arm 116 is rotated back to the first position so as toextend over container assembly 16. Rotational assembly 48 is thensecurely coupled with housing 124 on support arm 116 (FIG. 5) followingwhich drive shaft 17 (FIG. 3) is advanced through motor mount 138 andinto impeller assembly 40 so as to engage with hub 54 and impeller 64.

Once drive shaft 17 is properly positioned, support housing 14 can berotated back to its vertical or other desired operating position.Container 18 can then be filed with media or other processing fluids andcomponents. Where container 18 is functioning as a bioreactor orfermentor, cells or microorganisms along with nutrients and otherstandard components can be added to container. Before or after addingthe different components, drive motor assembly 15 can be activatedcausing drive shaft 17 to rotate impeller 64 and thereby mix or suspendthe fluid within container 18. Once the fluid processing is complete,the fluid can be drained out through drain line 39. Support housing 14can be tilted to facilitate draining all of the fluid out of container18. The reverse of the above process can then be used to removecontainer assembly 16 from support housing 14.

In one embodiment of the present invention, means are provided formixing the fluid within container 18 without movement of support housing14. Impeller assembly 40 in conjunction with drive shaft 17, asdiscussed above, is one example of such means for mixing. It isappreciated, however, that impeller assembly 40 and drive shaft 17 canhave different configurations. For example, two or more impellers can bespaced apart along tubular connector 42. Drive shaft 17 can engage eachof the impellers but it is not required.

In another alternative embodiment, it is appreciated that drive shaft 17need not directly engage each of the hub 54 and impeller 64. Forexample, drive shaft 17 could engage hub 54 but not impeller 64. In thisembodiment, rotation of hub 54 would cause rotation of tubular connector42 which would then indirectly cause rotation of impeller 64. Likewise,drive shaft 17 need not engage with hub 54. In this example, therotation of impeller 64 by drive shaft 17 causes the rotation of tubularconnector 42 which then indirectly causes rotation of hub 54. The aboveembodiments can be more commonly used when tubular connector 42 is rigidor substantially rigid but can also be used when tubular connector 42 isflexible.

In another alternative embodiment of the means for mixing, tubularconnector 42 can be eliminated. For example, depicted in FIG. 7 is acontainer assembly 16A that includes container 18. A dynamic seal 207 ismounted on upper end wall 33. A rigid drive shaft 209 passes throughdynamic seal 207 and has a first end 208 disposed outside of container18 and an opposing second end 210 disposed within container 18. Dynamicseal 207 enables drive shaft 209 to freely rotate relative to container18 while forming an aseptic seal about drive shaft 209. A driver portion212 or some other engaging surface is formed at first end 208 so that amotor assembly can engage with and rotate drive shaft 209. The motorassembly could be secured to support housing 14 or could be mounted on aseparate adjacent structure. Mounted on second end 210 of drive shaft209 is impeller 64.

In another embodiment of the means for mixing, impeller 64 could bereplaced by paddles or other mixing elements that mix by pivoting,swirling, rotating or the like. A mixing element could also be used thatis repeatedly raised and lowered within container 18 to facilitate fluidmixing. One example of such a mixing element is disclosed in U.S. Pat.No. 6,908,223 which issued Jun. 21, 2005. Impeller 64 and related driveshaft 17 could also be replaced by a magnetically driven impeller ormixing element disposed within container 18. Where a magnetic mixingelement is disposed within container 18, a magnetic driver could besecured to support housing 14, such as on the bottom surface of floor 88(FIG. 1). The external magnet driver would facilitate rotation or othermovement of the magnetic mixing element within container 18. As usedherein, the term “mixing element” is broadly intended to coverimpellers, paddles, magnetic stir bars, vertical mixers, other mixingbars and the like that can mix fluid within container 18 without themovement of support housing 14.

The present invention also includes means for mixing fluid containedwithin container 18 by repeatedly moving support housing 14 andcontainer 18 contained therein. For example, depicted in FIG. 8 is oneembodiment of a fluid mixing system 10A. Like elements between fluidmixing system 10 and 10A are identified by like reference characters.Likewise, all prior discussions and alternatives previously discussedwith fluid mixing system 10 are also applicable to fluid mixing system10A. Fluid mixing system 10A is substantially identical to fluid mixingsystem 10 except that a motor 220 is mounted on brace 192A and engageswith axle 196. Motor 220 is electrically coupled with a controller 222.Controller 222 operates motor 220 so that motor 220 continuously pivotssupport housing 14 about axis 197 between a forward tilt position asshown in FIG. 9 and a rearward tilt position as shown in FIG. 10. Thisrepeated tilting or rocking of support housing 14 causes fluid withincontainer 18 to mix. In other embodiments, impeller 64 and the otherrelated mixing components can be eliminated and mixing within container18 can be accomplished only by rocking or otherwise moving supporthousing 14.

The tilting or rocking of support housing 14 can be accomplished byactivating motor 220 until support housing 14 pivots over a certainangle and then deactivating motor 220 so that support housing 14 swingsback under gravitational force. Alternatively, motor 220 can be operatedto rotate axle 196 is a first direction and then rotate axle 196 in anopposing second direction. In yet other embodiments, a mechanicallinkage can be used to produce the discussed rocking while allowingcontinual motor motion in a single direction. In the depictedembodiment, drive motor assembly 15, drive shaft 17, and impellerassembly 40 can be eliminated. Alternatively, impeller assembly 40 andthe related components can be used in conjunction with motor 220. Forexample, motor 220 can be used to mix small volumes of fluid withincontainer assembly 16 by rocking support housing 13 while impellerassembly 40 or other mixing elements can be used to mix larger volumesof fluid within container assembly 16 without required movement ofsupport housing 13. The different types of mixing systems can also beused concurrently. As such, the type of mixing used can change as thevolume of fluid increases within container assembly 16.

When mixing fluid by rocking, the tilting of support housing 14 istypically made over an angle tilted forward and back from vertical thatis typically at least 5°, 10° or 15° from vertical. For example, supporthousing 14 can tilt 10° forward and 10° backward. The angle of tiltduring mixing is commonly in a range between about 5° to about 45° fromvertical with about 10° to about 30° from vertical being more common.Other angles can also be used. It is appreciated that there are a numberof different mechanisms that can be used for continuously rockingsupport housing 14. For example, rather than using a motor that coupleswith axle 196, an arm, pulley system, gear assembly, or a variety ofother mechanisms can be mounted to the upper or lower end of supporthousing 14 for mechanically tilting support housing 14 back and forthabout axis 197. The above examples of mechanisms for rocking supporthousing 14 are all examples of means for repeatedly rocking supporthousing 14 between the forward tilt position and the rearward tiltposition.

Depicted in FIG. 11 is a perspective view of a fluid mixing system 10B.Like elements between fluid mixing systems 10, 10A and 10B areidentified by like reference characters. Likewise, all prior discussionand alternatives previously discussed with fluid mixing systems 10 and10A are also applicable to fluid mixing system 10B. Fluid mixing system10B is substantially identical to fluid mixing system 10A except thatfluid mixing system 10B includes an adjustable mounting rack 230 thatsecures drive motor assembly 15 to support housing 14. Mounting rack 230permit the selective adjustment of the angle at which drive shaft 17 andimpeller 64 mounted on the end thereof project into container 18.Specifically, mounting rack 230 comprises a base 232 mounted to sidewall82 of support housing 14 at or towards upper end 84. An arm 234 ispivotally mounted to base 232 by a hinge 236. Drive motor 112 is mountedon arm 234 so that drive motor assembly 15 rotates concurrently with arm234 about hinge 236.

Arm 234 can be selectively pivoted about hinge 236 so that a centrallongitudinal axis 238 that extends through passage 139 of motor mount138 (axis 238 also extending along the length of drive shaft 17 whendrive shaft 17 is received within motor mount 138) can be moved from afirst position as shown in FIG. 11 to a second position as shown in FIG.12. In the first position, axis 238 is aligned with longitudinal axis 98of chamber 92 of support housing 14. As such, drive shaft 17 andimpeller 64 are centrally disposed within container 18 during operationand are vertically disposed when support housing 14 is verticallyorientated. Mixing system 10 shown in FIG. 1 produces the sameorientation for drive shaft 17 and impeller 64.

In the second position shown in FIG. 12, drive motor assembly 15 istilted concurrently with arm 234 so that axis 238 is tilted relative toaxis 98 at an angle α₂. Drive shaft 17 and impeller 64 (FIG. 5) are thusalso disposed at angle α₂ when within container 18. The angle α₂ istypically in a range between about 10° to about 30° or about 5° to about20° which angle can also be relative to vertical. Other angles can alsobe used. It can be desirable to adjust the angle of orientation ofimpeller 64 to achieve optimal mixing for different impellers atdifferent speeds. For example, at slower speeds it can be desirable totilt impeller 64 to improve mixing, such as by increasing turbulentflow. In view of the foregoing, it is appreciated that support arm 116can selectively rotate about an axis that is substantially parallel tolongitudinal axis 98 (FIG. 6) and can also selectively rotate about anaxis that is substantially perpendicular to longitudinal axis 98 (FIG.12).

With reference to FIG. 11, base 232 of mounting rack 230 is movablymounted to a rail 244 secured to sidewall 82 of support housing 14. Rail244 typically extends along sidewall 82 parallel to longitudinal axis 98so that when support housing 14 is vertically orientated, mounting rack230 can be selectively moved vertically up and down along supporthousing 14 and then locked at a desired location. The movement ofmounting rack 230 also correspondingly moves drive motor assembly 15,which is coupled to mounting rack 230, which can in turn correspondinglymove drive shaft 17 and impeller assembly 40 when they are coupled todrive motor assembly 15. The movement of mounting rack 230 can thusadjust the vertical position of impeller 64 within container 18 or canadjust the spacing between floor 88 of support housing 14 and impeller64. The vertical positioning of impeller 64 can be used to achieveoptimal mixing of different levels of fluid within container 18.

Depicted in FIG. 13 is a perspective view of a fluid mixing system 10C.Like elements between fluid mixing systems 10, 10A and 10B areidentified by like reference characters. Likewise, all prior discussionsand alternatives previously discussed with regard to fluid mixingsystems 10, 10A and 10B are also applicable to like elements of fluidmixing system 10C. Fluid mixing system 10C is substantially identical tofluid mixing system 10B except that support stand 12 and motor 220 havebeen removed and support housing 14 now rests on a shaker table 250.Shaker table 250 comprises a base 252 and a platform 254 supported onbase 252. Base 252 includes a drive mechanism that reciprocally movesplatform 254 in one or two dimensions in a horizontal plane. Acontroller 256 can be used to activate shaker table 250 and control therate of reciprocal movement of platform 254. It is appreciated thatshaker tables are known in the art and that any off the shelf or customshaker table configured to handle the load capacity of support housing14, container assembly 16 and the related fluid can be used.

Support housing 14 rests on platform 254 of shaker table 250 so thatfluid within container assembly 16 can be selectively mixed when shakertable 250 is activated. As previously discussed with regard to usingmotor 220 to rock support housing 14, it is appreciated that shakertable 250 would more commonly be used for mixing low volumes of fluidwithin container assembly 16 and that impeller 64 or other mixingelements would be used for mixing the fluid within container assembly 16for larger volumes of fluid. In still other embodiments other mechanismscan be used for mixing fluid within container assembly 16 by movement ofsupport housing 14. For example, support housing 14 can be mounted on atable that reciprocally or continuously tilts, pivots, swivels or thelike so as to produce mixing of the fluid within container assembly 16.

It is appreciated that mixing systems 10A-10C, which each have twodifferent types of mixing mechanisms, can achieve a number of uniquebenefits, especially when they are being used as a bioreactor orfermentor. For example, as previously mentioned, when growing biologicalcultures it is desirable that the culture be continuously andhomogeneously mixed so as to achieve proper feeding and mass transfer ofgases within the culture. Proper mixing can be achieved for low volumesof culture or fluids within container assembly 16 by simply movingsupport housing 14, such as in a reciprocal of continuous fashion. Aspreviously discussed, the movement of support housing 14 needed formixing can be accomplished in a variety of different manners such asrocking, shaking, swiveling, tilting or otherwise moving support housing14. What constitutes a “low” volume of fluid is dependent in part on thesize and shape of container assembly 16. The concept is that forrelatively large container assemblies 16 containing only a very lowvolume of fluid, impeller 64 or other mixing elements may not properlyfunction for mixing the fluid. For example, impeller 64 may not reachthe fluid for mixing or, if the impeller does reach the fluid, theimpeller may be so large relative to the volume of fluid that operationof impeller 64 would create splashing or apply other unwanted shearforces on the culture which would be detrimental to the culture. Thesame can also be true for the other types of mixing elements. Incontrast, mixing by rocking, shaking, tilting or the like of supporthousing 14/container assembly 16 can achieve the desired mixing withoutapplying unwanted shear forces.

As the culture grows, additional media and other components are added,thereby increasing the volume of the fluid. The media can be added in aslow continuous fashion or at staged intervals. Mixing by movement ofsupport housing 14/container assembly 16 can be used until the volume offluid within container assembly 16 gets so large that that form ofmixing can no longer achieve the desired mixing rate. At that stage,movement of support housing 14/container assembly 16 for mixing can bestopped and mixing by impeller 64 or other mixing element withincontainer assembly 16 can be activated. In some embodiments, it may bedesirable to have a gradual transition between the two different mixingtechniques. For example, mixing by impeller 64 may be gradually startedat low speeds while mixing by movement of support housing 14/containerassembly 16 is maintained. As the culture volume further increases, thespeed of rotation of impeller 64 can be gradually increased while themixing by movement of support housing 14/container assembly 16 isgradually decreased until eventually stopped. As the volume of culturecontinues to increase within container assembly 16, it may be necessaryto adjust the vertical height, orientation and/or speed of impeller 64within container assembly 16 to maintain the desired mixing for thecorresponding volume. This adjustment can be achieved as previouslydiscussed.

Once the culture has reached a desired batch size, the culture may begradually removed from container assembly 16 as needed. As the cultureis removed and the volume decreases, the mixing conditions can bereversed. That is, as the volume decreases, the mixing by impeller 64 orother mixing element within container assembly 16 can be slowed orstopped while mixing by moving support housing 14/container assembly 16is increased.

In view of the foregoing, embodiments of the present invention producedesired mixing of the culture over a wide range of volumes whileeliminating the risk of unwanted shear forces. Furthermore, the culturecan be grown over a wide range of volumes within a single container.This eliminates or reduces the number of different containers that theculture needs to be transferred into during both the growth stage andthe removal stage. By reducing the number of transfers betweencontainers, there is less down time in processing, less risk ofcontamination, less material waste, and fewer man hours required. As aresult, the culture product is produced safer and with lower productioncosts.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

What is claimed is:
 1. A method for mixing a fluid comprising:dispensing a first volume of a fluid into a flexible container, theflexible container being at least partially disposed within a chamber ofa support housing; repeatedly moving the support housing and theflexible container contained therein so as to mix the first volume offluid within the flexible container; adding further fluid into theflexible container after moving the support housing to form a secondvolume of fluid; and manipulating a mixing element within the flexiblecontainer so as to mix the second volume of fluid.
 2. The method asrecited in claim 1, wherein repeatedly moving the support housingcomprises repeatedly rocking, shaking, tilting, or swiveling the supporthousing.
 3. The method as recited in claim 1, wherein manipulating themixing element comprises rotating an impeller or magnetic stir barwithin the flexible container.
 4. The method as recited in claim 1,wherein manipulating the mixing element comprises pivoting, swiveling,or vertically raising and lowering the mixing element within theflexible container.
 5. The method as recited in claim 1, wherein thestep of repeatedly moving the support housing occurs withoutmanipulating the mixing element within the flexible container.
 6. Themethod as recited in claim 1, wherein the step of manipulating themixing element further comprises concurrently, repeatedly moving thesupport housing and the flexible container contained therein.
 7. Themethod as recited in claim 1, wherein the step of manipulating themixing element occurs without repeatedly moving the support housing andthe flexible container contained therein.
 8. The method as recited inclaim 1, wherein the first volume of fluid comprises cells ormicroorganisms and the further fluid is added based on the growth of thecells or microorganisms within the flexible container.
 9. The method asrecited in claim 1, further comprising sparging a gas into the firstvolume of the fluid.
 10. The method as recited in claim 1, wherein theflexible container comprises a flexible bag that is comprised of one ormore sheets of a polymeric film.
 11. The method as recited in claim 1,wherein the mixing element comprises an impeller and the method furthercomprises adjusting a location of the impeller within the flexiblecontainer based on the volume of fluid within the flexible container.12. A method for mixing a fluid comprising: tilting a support housingthat comprises a sidewall that encircles a chamber, an access openingformed at a first end of the sidewall, and a floor disposed at a secondend of the sidewall, an axis extending through the chamber so as to passthrough the floor and the access opening, the support housing beingtilted from a first position wherein the axis is vertically oriented toa second position wherein the axis is at least 45° from vertical;inserting a container assembly into the chamber of the support housingwhen the support housing is in the second position, the containerassembly comprising a flexible bag bounding a compartment adapted tohold a fluid; moving the support housing containing the containerassembly back to the first position; delivering a fluid into thecompartment of the flexible bag; and mixing the fluid within thecompartment of the flexible bag.
 13. The method as recited in claim 12,wherein the step of mixing the fluid comprises manipulating a mixingelement located within the compartment of the flexible bag.
 14. Themethod as recited in claim 13, further comprising: after the step oftilting the support housing, moving an arm from a first position whereinthe arm projects over the access opening so that the axis passes throughthe arm to a second position wherein the arm is spaced apart from theaxis; and moving the arm from the second position back to the firstposition after inserting the container assembly into the chamber of thesupport housing.
 15. The method as recited in claim 14, furthercomprising: coupling a drive shaft to the arm and to the mixing element;and rotating the drive shaft.
 16. The method as recited in claim 12,wherein the step of mixing the fluid comprises repeatedly moving thesupport housing and the flexible container contained therein.
 17. Themethod as recited in claim 16, wherein the step of repeatedly moving thesupport housing comprises activating a motor so as to cause the supporthousing to repeatedly rock between a forward tilt position and anopposing rearward tilt position.
 18. The method as recited in claim 12,wherein the step of tilting the support housing comprises tilting thesupport housing so that the axis is at least 75° from vertical when inthe second position.